Quinones, Mar ORCID: 0000-0003-0180-2147, Al-Massadi, Omar ORCID: 0000-0003-0645-6159, Folgueira, Cintia ORCID: 0000-0003-3803-9149, Bremser, Stephan, Gallego, Rosalia, Torres-Leal, Leonardo, Haddad-Tovolli, Roberta, Garcia-Caceres, Cristina, Hernandez-Bautista, Rene, Lam, Brian Y. H., Beiroa, Daniel ORCID: 0000-0003-1862-1668, Sanchez-Rebordelo, Estrella ORCID: 0000-0002-7654-1618, Senra, Ana, Malagon, Jose A., Valerio, Patricia, Fondevila, Marcos F., Ferno, Johan, Malagon, Maria M., Contreras, Raian, Pfluger, Paul, Bruening, Jens C., Yeo, Giles, Tschoep, Matthias, Dieguez, Carlos, Lopez, Miguel ORCID: 0000-0002-7823-1648, Claret, Marc ORCID: 0000-0001-7766-9296, Kloppenburg, Peter, Sabio, Guadalupe ORCID: 0000-0002-2822-0625 and Nogueiras, Ruben ORCID: 0000-0002-9976-9930 (2018). p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

p53 is a well-known tumor suppressor that has emerged as an important player in energy balance. However, its metabolic role in the hypothalamus remains unknown. Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity. AgRP-specific ablation of p53 resulted in increased hypothalamic c-Jun N-terminal kinase (JNK) activity before the mice developed obesity, and central inhibition of JNK reversed the obese phenotype of these mice. The overexpression of p53 in the ARC or specifically in AgRP neurons of obese mice decreased body weight and stimulated BAT thermogenesis, resulting in body weight loss. Finally, p53 in AgRP neurons regulates the ghrelin-induced food intake and body weight. Overall, our findings provide evidence that p53 in AgRP neurons is required for normal adaptations against diet-induced obesity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Quinones, MarUNSPECIFIEDorcid.org/0000-0003-0180-2147UNSPECIFIED
Al-Massadi, OmarUNSPECIFIEDorcid.org/0000-0003-0645-6159UNSPECIFIED
Folgueira, CintiaUNSPECIFIEDorcid.org/0000-0003-3803-9149UNSPECIFIED
Bremser, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallego, RosaliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres-Leal, LeonardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haddad-Tovolli, RobertaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Caceres, CristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez-Bautista, ReneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lam, Brian Y. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beiroa, DanielUNSPECIFIEDorcid.org/0000-0003-1862-1668UNSPECIFIED
Sanchez-Rebordelo, EstrellaUNSPECIFIEDorcid.org/0000-0002-7654-1618UNSPECIFIED
Senra, AnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malagon, Jose A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Valerio, PatriciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fondevila, Marcos F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferno, JohanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malagon, Maria M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Contreras, RaianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfluger, PaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeo, GilesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tschoep, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dieguez, CarlosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez, MiguelUNSPECIFIEDorcid.org/0000-0002-7823-1648UNSPECIFIED
Claret, MarcUNSPECIFIEDorcid.org/0000-0001-7766-9296UNSPECIFIED
Kloppenburg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sabio, GuadalupeUNSPECIFIEDorcid.org/0000-0002-2822-0625UNSPECIFIED
Nogueiras, RubenUNSPECIFIEDorcid.org/0000-0002-9976-9930UNSPECIFIED
URN: urn:nbn:de:hbz:38-176059
DOI: 10.1038/s41467-018-05711-6
Journal or Publication Title: Nat. Commun.
Volume: 9
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
AGOUTI-RELATED PEPTIDE; ADIPOSE-TISSUE THERMOGENESIS; REGULATES FOOD-INTAKE; CONNECTS ER STRESS; ENERGY-BALANCE; ENDOPLASMIC-RETICULUM; HYPOTHALAMIC AMPK; GLUCOSE-HOMEOSTASIS; POMC NEURONS; METABOLIC-REGULATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17605

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